Version May 2024
Breast cancer, adjuvant therapy:
Adjuvant treatment following 2 to 3 years of tamoxifen: Postmenopausal patients: Oral: 25 mg once daily (following 2 to 3 years of tamoxifen therapy) for a total duration of 5 years of endocrine therapy (in the absence of recurrence or contralateral breast cancer).
First-line adjuvant treatment (off-label use): Postmenopausal patients: Oral: 25 mg once daily for 5 years (Ref).
Adjuvant endocrine therapy (in combination with ovarian function suppression) for hormone receptor–positive high-risk disease (off-label use): Premenopausal patients: Oral: 25 mg once daily (in combination with ovarian function suppression [OFS]) for ~5 years; if chemotherapy was administered, initiate exemestane after chemotherapy completion, and, if chemotherapy was not administered, initiate exemestane 6 to 8 weeks after OFS initiation (Ref).
Duration of adjuvant endocrine therapy: American Society of Clinical Oncology (ASCO) guidelines for adjuvant endocrine therapy for women with hormone receptor–positive (HR+) breast cancer (focused update) recommend a duration of 5 to 10 years of adjuvant endocrine therapy; some patients may be appropriate candidates for extended aromatase inhibitor (AI) therapy for up to a total of 10 years based on disease recurrence risk and nodal disease status. Refer to the guidelines for specific recommendations based on menopausal status and tolerability (Ref). In a phase 3 study with another AI (letrozole), treatment with an additional 5 years of AI therapy (for a total of 10 years of endocrine therapy) demonstrated a significantly improved rate of disease-free survival and a decreased risk of disease recurrence and contralateral breast cancer (when compared to placebo); although, overall survival was not significantly different between groups, and bone-related adverse events occurred more frequently with letrozole versus placebo (Ref).
Breast cancer, advanced: Postmenopausal patients: Oral: 25 mg once daily; continue until tumor progression.
Off-label combination: Breast cancer, hormone receptor–positive (HR+), advanced, in patients with recurrence or progression on prior endocrine therapy: Postmenopausal patients: Oral: 25 mg once daily (in combination with everolimus) until disease progression or unacceptable toxicity (Ref).
Note: The ASCO guideline update for endocrine treatment and targeted therapy for HR+, human epidermal growth factor receptor 2-negative metastatic breast cancer supports the use of an AI in combination with a CDK4/6 inhibitor for the initial treatment of HR+ metastatic breast cancer in postmenopausal patients, and in premenopausal patients when combined with chemical ovarian function suppression (Ref).
Breast cancer in male patients, hormone receptor–positive (off-label use): Note: Should be used in combination with a gonadotropin-releasing hormone agonist/antagonist (Ref).
Adjuvant therapy (alternative agent): May be used as adjuvant therapy in male patients with HR+ breast cancer with a contraindication to tamoxifen. Oral: 25 mg once daily (Ref). ASCO guidelines for management of male breast cancer recommend an initial duration of 5 years of adjuvant endocrine therapy; if there still is a high risk of recurrence, 5 additional years of endocrine therapy may be offered if the initial 5 years of adjuvant therapy have been completed and tolerated (Ref).
Advanced or metastatic disease: Oral: 25 mg once daily until disease progression or unacceptable toxicity (Ref). Endocrine therapy for males with advanced or metastatic, HR+, HER2-negative breast cancer may be sequenced as in females (Ref).
Breast cancer, risk reduction (off-label use): Postmenopausal patients ≥35 years of age at increased risk of developing breast cancer: Oral: 25 mg once daily for 5 years (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
No adjustment necessary (although the safety of chronic doses in patients with moderate-to-severe renal impairment has not been studied, dosage adjustment does not appear necessary).
No adjustment necessary (although the safety of chronic doses in patients with moderate-to-severe hepatic impairment has not been studied, dosage adjustment does not appear necessary).
Decreased bone mineral density: Manage bone density loss as clinically indicated.
Vitamin D deficiency: Supplement as clinically indicated.
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults.
>10%:
Cardiovascular: Hypertension (5% to 15%)
Dermatologic: Alopecia (15%), hyperhidrosis (4% to 12%)
Endocrine & metabolic: Hot flash (13% to 33%)
Gastrointestinal: Nausea (9% to 18%)
Hematologic & oncologic: Lymphocytopenia (grades 3/4: 20%)
Hepatic: Increased serum alkaline phosphatase (14% to 15%)
Nervous system: Depression (6% to 13%), fatigue (8% to 22%), headache (7% to 13%), insomnia (11% to 12%), pain (13%)
Neuromuscular & skeletal: Arthralgia (15%)
1% to 10%:
Cardiovascular: Acute myocardial infarction (≤2%), angina pectoris (≤2%), chest pain (2% to 5%), edema (≤7%), ischemic heart disease (≤2%), lower extremity edema (≤7%), peripheral edema (≤7%)
Dermatologic: Dermatitis (8%), pruritus (2% to 5%), skin rash (2% to 5%)
Endocrine & metabolic: Increased gamma-glutamyl transferase (grades 3/4: 3%), weight gain (8%)
Gastrointestinal: Abdominal pain (6%), anorexia (6%), constipation (5%), diarrhea (4% to 10%), dyspepsia (2% to 5%), increased appetite (3%), vomiting (7%)
Genitourinary: Urinary tract infection (2% to 5%)
Hematologic & oncologic: Lymphedema (2% to 5%)
Hepatic: Increased serum bilirubin (5% to 7%)
Infection: Infection (2% to 5%)
Nervous system: Anxiety (10%), carpal tunnel syndrome (2%), confusion (2% to 5%), dizziness (8% to 10%), hypoesthesia (2% to 5%), paresthesia (3%), tumor pain (8%)
Neuromuscular & skeletal: Asthenia (6%), back pain (9%), limb pain (9%), muscle cramps (2%), myalgia (6%), osteoarthritis (6%), osteoporosis (5%), pathological fracture (4%), skeletal pain (2% to 5%)
Ophthalmic: Visual disturbance (5%)
Renal: Increased serum creatinine (6%)
Respiratory: Bronchitis (2% to 5%), cough (6%), dyspnea (10%), flu-like symptoms (6%), pharyngitis (2% to 5%), rhinitis (2% to 5%), sinusitis (2% to 5%), upper respiratory tract infection (2% to 5%)
Miscellaneous: Fever (5%)
<1%:
Cardiovascular: Heart failure, thromboembolism
Gastrointestinal: Gastric ulcer
Genitourinary: Endometrial hyperplasia, endometrial polyps
Nervous system: Neuropathy
Neuromuscular & skeletal: Abnormal bone growth (osteochondrosis), tenosynovitis (stenosans [trigger finger])
Frequency not defined:
Hepatic: Increased serum transaminases
Neuromuscular & skeletal: Decreased bone mineral density
Postmarketing:
Dermatologic: Acute generalized exanthematous pustulosis, urticaria
Hepatic: Cholestatic hepatitis, hepatitis
Hypersensitivity: Hypersensitivity reaction
Known hypersensitivity to exemestane or any component of the formulation
Concerns related to adverse effects:
• Decreased bone mineral density: Due to decreased circulating estrogen levels, exemestane is associated with a reduction in bone mineral density over time. Decreases (from baseline) in lumbar spine and femoral neck density have been observed (when compared to tamoxifen or placebo in studies where concomitant use of bisphosphonates, calcium and vitamin D were not allowed).
• Lymphopenia: Grade 3 or 4 lymphopenia has been observed with exemestane, although most patients had preexisting lower grade lymphopenia; some patients improved or recovered while continuing exemestane. Lymphopenia did not result in a significant increase in viral infections, and no opportunistic infections were observed.
• Lab parameters: Elevations of AST, ALT, alkaline phosphatase, and gamma glutamyl transferase >5 times ULN have been observed (rarely) in patients with advanced breast cancer; may be attributable to underlying liver and/or bone metastases. In patients with early breast cancer, elevations of bilirubin, alkaline phosphatase, and serum creatinine were more common with exemestane treatment than with tamoxifen or placebo.
Concurrent drug therapy issues:
• Estrogen-containing drugs: Exemestane should not be administered concurrently with estrogen-containing medications.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Aromasin: 25 mg
Generic: 25 mg
Yes
Tablets (Aromasin Oral)
25 mg (per each): $46.05
Tablets (Exemestane Oral)
25 mg (per each): $3.60 - $20.23
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Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Aromasin: 25 mg [contains methyl hydroxybenzoate, polysorbate 80]
Generic: 25 mg
Administer after a meal.
Hazardous agent (NIOSH 2016 [group 1]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).
Breast cancer:
Adjuvant treatment of estrogen receptor–positive early breast cancer in postmenopausal patients who have received 2 to 3 years of tamoxifen (for completion of a total of 5 consecutive years of adjuvant hormonal therapy).
Treatment of advanced breast cancer in postmenopausal patients whose disease has progressed following tamoxifen therapy.
Breast cancer, high-risk, hormone receptor–positive, adjuvant endocrine therapy (in combination with ovarian function suppression) in premenopausal patients; Breast cancer, early, estrogen receptor–positive, first-line adjuvant treatment in postmenopausal patients; Breast cancer in male patients, hormone receptor–positive; Risk reduction for invasive breast cancer in postmenopausal patients
Aromasin may be confused with Arimidex
Exemestane may be confused with estramustine.
Substrate of CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
CYP3A4 Inducers (Moderate): May decrease the serum concentration of Exemestane. Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May decrease the serum concentration of Exemestane. Management: Increase the exemestane dose to 50 mg once daily in patients receiving concurrent strong CYP3A4 inducers. Monitor patients closely for evidence of toxicity or inadequate clinical response. Risk D: Consider therapy modification
Estrogen Derivatives: May diminish the therapeutic effect of Exemestane. Risk X: Avoid combination
Levomethadone: Aromatase Inhibitors may increase the serum concentration of Levomethadone. Risk C: Monitor therapy
Methadone: Aromatase Inhibitors may increase the serum concentration of Methadone. Risk C: Monitor therapy
St John's Wort: May decrease the serum concentration of Exemestane. Management: Increase the exemestane dose to 50 mg once daily in patients receiving St John's wort. Monitor patients closely for evidence of toxicity or inadequate clinical response. Risk D: Consider therapy modification
AUC and Cmax were increased by 59% and 39%, respectively, when exemestane was administered with a high-fat breakfast. Management: Administer after a meal.
Pregnancy testing within 7 days prior to initiation of exemestane is recommended for patients who could become pregnant. Patients who could become pregnant should use effective contraception during treatment and for 1 month after the final exemestane dose.
Based on the mechanism of action and data from animal reproduction studies, exemestane is expected to cause fetal harm if administered to a pregnant patient.
It is not known if exemestane is present in breast milk.
Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during treatment and for 1 month after the final exemestane dose.
25-hydroxy vitamin D levels (at baseline). Assess bone mineral density at baseline in patients with, or at risk for osteoporosis; monitor for bone density loss during exemestane therapy. Pregnancy testing within 7 days prior to initiation for patients who could become pregnant.
Cardiovascular monitoring for patients with breast cancer: Comprehensive assessment prior to treatment including a history and physical examination, screening for cardiovascular disease risk factors such as hypertension, diabetes, dyslipidemia, obesity, and smoking; estimate 10-year cardiovascular disease risk in patients without cardiovascular disease at baseline; assess cardiovascular risk annually in patients with a high 10-year risk (ASCO [Armenian 2017]; ESC [Lyon 2022]).
Exemestane is an irreversible, steroidal aromatase inactivator. It is structurally related to androstenedione, and is converted to an intermediate that irreversibly blocks the active site of the aromatase enzyme, leading to inactivation ("suicide inhibition") and thus preventing conversion of androgens to estrogens in peripheral tissues. Significantly lowers circulating estrogens in postmenopausal breast cancers where growth is estrogen-dependent.
Absorption: Rapid and moderate (~42%) following oral administration; AUC and Cmax increased by 59% and 39%, respectively, following a high-fat breakfast (compared to fasted state).
Distribution: Extensive into tissues.
Protein binding: 90%, primarily to albumin and α1-acid glycoprotein.
Metabolism: Extensively hepatic; oxidation (CYP3A4) of methylene group, reduction of 17-keto group with formation of many secondary metabolites; metabolites are inactive.
Half-life elimination: ~24 hours.
Time to peak: Patients with breast cancer: 1.2 hours.
Excretion: Urine (<1% as unchanged drug, 39% to 45% as metabolites); feces (36% to 48%).
Altered kidney function: AUC was ~3 times higher in those with moderate or severe renal impairment compared to subjects with normal renal function.
Hepatic function impairment: AUC was ~3 times higher in those with moderate or severe hepatic impairment compared to subjects with normal hepatic function.
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